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Journal of Bacteriology, December 2001, p. 7354-7364, Vol. 183, No. 24
0021-9193/01/$04.00+0   DOI: 10.1128/JB.183.24.7354-7364.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

relA-Independent Amino Acid Starvation Response Network of Streptococcus pyogenes

Kerstin Steiner and Horst Malke*

Institute for Molecular Biology, Friedrich Schiller University Jena, D-07745 Jena, Germany

Received 2 July 2001/Accepted 24 September 2001

Streptococcus pyogenes (group A streptococcus [GAS]), a multiple-amino-acid-auxotrophic human pathogen, may face starvation for essential amino acids during various stages of the infection process. Since the response of GAS to such conditions is likely to influence pathogenetic processes, we set out to identify by transcriptional analyses genes and operons that are responsive to amino acid starvation and examined whether functionally meaningful response patterns can be ascertained. We discovered that GAS are capable of mounting a relA-independent amino acid starvation response that involves transcriptional modulation of a wide array of housekeeping genes as well as accessory and dedicated virulence genes. Housekeeping genes that were upregulated during starvation of both wild-type and relA mutant strains included the newly identified T-box members of the aminoacyl-tRNA synthetase genes, the genes for components of the tmRNA-mediated peptide tagging and proteolysis system for abnormal proteins (ssrA, smpB, clpP, and clpC), and the operons for the dnaK and groE groups of molecular chaperones. In addition to upregulation of the genes for oligopeptide permease (opp), intracellular peptidase (pepB), and the two-component regulator covRS reported previously (K. Steiner and H. Malke, Mol. Microbiol. 38:1004-1016, 2000), amino acid starvation stimulated the transcription of the growth phase-associated, virulence-regulatory fas operon, the streptolysin S operon (sag), and the gene for autoinducer-2 production protein (luxS). A prominent feature of operons exhibiting internal transcriptional termination (opp, fas, and sag) was starvation-promoted full-length transcription, a mechanism that improves the efficacy of these systems by increasing the level of coordinate transcription of functionally related genes. Based on these results, a regulatory network with feedback mechanisms is proposed that counteracts the stringent response, links the levels of key rate-limiting enzymes to virulence gene expression, and enables the organism in a dynamic way to take advantage of protein-rich environments provided by its human host. As several of the affected target genes are controlled by more than one regulator, fine modulation may result in accordance with the demands imposed by ecologically different colonization sites upon the adaptive capacity of the pathogen.

* Corresponding author. Mailing address: FSU Jena, Institute for Molecular Biology, Winzerlaer Strasse 10, D-07745 Jena, Germany, Phone: 49 3641 657530. Fax: 49 3641 657520. E-mail: hmalke{at}imb-jena.de.

Journal of Bacteriology, December 2001, p. 7354-7364, Vol. 183, No. 24
0021-9193/01/$04.00+0   DOI: 10.1128/JB.183.24.7354-7364.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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